Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Human Genome Research Institute (NHGRI/NIH), (http://genome.gov) on behalf of the NIH. Participating Institutes: National Human Genome Research Institute (NHGRI) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institute on Drug Abuse (NIDA) National Institute of Neurological Disorders and Stroke (NINDS) Office of AIDs Research (OAR) Fogarty International Center (FIC) Office of Strategic Coordination (Common Fund)
Funding Opportunity Title	Human Heredity and Health in Africa (H3Africa): Collaborative Centers (U54)
Activity Code	U54 Specialized Center- Cooperative Agreements
Announcement Type	New
Related Notices	August 22, 2012 - This RFA has been reissued as RFA-RM-12-006. June 13, 2012 - See Issuance of RFA-RM-12-005: Human Heredity and Health in Africa (H3Africa): Ethical, Legal, and Societal Issues (ELSI) Research Program (U01). May 25, 2012 - See Notice NOT-RM-12-024. Notice of Intent to Publish Human Heredity and Health in Africa (H3Africa): Collaborative Centers FOA. November 16, 2011 - See Notice NOT-RM-12-006. Notice of Total Costs allowed. October 14, 2011 - See Notice NOT-RM-12-002. The purpose of this Notice is to revise the wording of the following passages; Section IV, 2. Page Limitations, Section IV, 2. Administration and Management, Section IV, 2. Under Collaborations and Section I, Part 2. October 14, 2011 - See Notice NOT-RM-12-004. The purpose of this Notice is to provide additional information to those applicants who plan to include an advisory committee. September 14, 2011 - See Companion RFA-RM-11-011, Human Heredity and Health in Africa (H3Africa): H3Africa Biorepository Grants(UH2/UH3).
Funding Opportunity Announcement (FOA) Number	RFA-RM-11-008
Companion FOA	RFA-RM-11-009, Human Heredity and Health in Africa (H3Africa): Research Grants (U01) RFA-RM-11-010, Human Heredity and Health in Africa (H3Africa): Bioinformatics Network (U41)
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310, 93.172, 93.279, 93.853, 93.989 93.865
FOA Purpose	This NIH Funding Opportunity Announcement (FOA), supported by funds from the NIH Common Fund (Common Fund) and participating NIH Institute(s) and Center(s), invites applications from foreign Institutions in African countries who wish to develop the study of genomic/genetic/environmental contributors of human health and disease within Africa, using cutting edge research tools to understand health and diseases affecting African populations more completely and increase capacity for biomedical research, in terms of building infrastructure (including data and research resources), genomic proficiency of researchers and numbers of trainees. In partnership with the Wellcome Trust, the H3Africa initiative is focused on supporting these efforts as part of an effort to promote sustainable research in Africa that will promote health and combat disease. The purpose of this FOA is to call for applications for research centers called H3Africa Collaborative Centers. Awards will focus on supporting research on the genetic/environmental contributors to health and disease in Africa that fall within the mission of the NIH, which is to seek fundamental knowledge about the nature and behavior of living systems and to apply that knowledge to enhance health, lengthen life, and reduce the burdens of illness and disability.

Posted Date	August 23, 2011
Letter of Intent Due Date	September 30, 2011
Application Due Date(s)	December 2, 2011
AIDS Application Due Date(s)	Not applicable
Scientific Merit Review	February/March, 2012
Advisory Council Review	May, 2012
Earliest Start Date(s)	July, 2012
Expiration Date	December 3, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. NIH will announce plans to transition the remaining programs in the NIH Guide to Grants and Contracts and on NIH’s Applying Electronically website.

Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Purpose

Low- and middle-income nations suffer over ninety percent of the world’s burden of premature mortality, as measured in lost years of life. These countries, constituting three-quarters of the world’s population, now must deal with a triple burden: the persistent cluster of infectious diseases, malnutrition, and a growing incidence of chronic disease and disabilities due to increased life spans and new risk exposures that accompany it. The NIH has a long-standing commitment to address both communicable and non-communicable diseases around the world through health research and training, and one of NIH’s stated priorities is enhancing efforts in global health. Genomics and other large-scale biological studies provide cutting-edge approaches to research on the genetic and environmental contributors to health and disease, the understanding of which will lead to unimagined advances in medical science and powerful new ways for improving human health. To maximize the impact on the health of people globally, advances in the fields of genetics/genomics/environmental studies must be integrated into the research conducted in developing countries, as well as into their medical education and health services. Notably, however, African researchers and populations are substantially underrepresented in genomics and environmental research endeavors. For example, it has been found, as documented in a recent review, that, worldwide, the majority of the thousands of genetic studies completed to date (about 75%) were conducted exclusively in populations of European descent and only a fraction of the studies done with non-European populations came from Africa (Rosenberg NA, Huang L, et al. (2010). Nat Rev Genet 11(5):356-366). The paradox of limited genomics research conducted in Africa and the centrality of contemporary African populations for our understanding of human evolution and population genetics has been widely noted.

While there are pockets of research excellence in genetics and environmental studies on the African continent done by African and other scientists, a limited number of individuals have the expertise to engage in this work compared to the overall population size and burden of disease there. It is the objective of the H3Africa Initiative to enhance the capability of African scientists and research institutions to use genomics and other powerful new approaches to address problems of African health and disease. Increasing African research capacity by building infrastructure, expanding the genomic proficiency of researchers, and increasing the number of well-trained individuals is essential to promote sustainable efforts to address the challenges to advancing health and combating disease in Africa. While focused on benefitting the people of Africa, such research may also be relevant to the health of individuals in the U.S. and other countries worldwide, particularly those of African descent. For example, many scientists believe that different environmental exposures for a population whose genetic architecture evolved in environments with a scarcity of available resources are an underlying contributor to disease in the U.S.

H3Africa is a partnership among the National Institutes of Health (NIH, USA), the Wellcome Trust (WT, UK), and the African Society of Human Genetics (AfSHG). A set of recommendations for H3Africa was developed by a pair of working groups, composed primarily of African scientific experts, who addressed the major scientific, ethical and practical issues in the development of a large-scale genomics research program in Africa. The working groups formulated a detailed proposal (which can be found in a white paper at www.h3africa.org) to address the goal of creating and sustaining a network of African Centers that could carry out training and research based on state-of-the-art genomics approaches. Through support for infrastructure development, training, and specific research projects, the working group recommendations were designed to catalyze genomics and environmental research concerning human diversity, health, and disease biology of particular relevance and benefit to African populations and societies. The proposal was discussed at a public meeting held in Cape Town, South Africa in March 2011 and the attendees ratified the white paper’s recommendations.

The research program described in this FOA (and a similar call for proposals from the Wellcome Trust http://www.wellcome.ac.uk/Funding/Biomedical-science/Funding-schemes/Strategic-awards-and-initiatives/wtvm052057.htm ) is a response to the disparities in research capacity noted above and is based, in significant part, on the recommendations of the H3Africa white paper and from discussions at the Cape Town meeting. The H3Africa Initiative aims to contribute to the establishment of a viable, productive, and eventually sustainable, African research infrastructure to study the genetic and environmental contributors to disease and health. It aims to do so through a combination of the leveraging of existing capacity, expertise and infrastructure with investment in new research, infrastructure-building and training efforts.

H3Africa has three interrelated, interdependent objectives. The first is to increase the human resources for conducting cutting-edge genomics-based research in Africa through training and enhanced collaborations within Africa and with the African scientific diaspora. The second is to support cutting-edge research that will not only generate important findings and discoveries, but will serve as a vehicle for research training and for the improvement of the research capacity of African laboratories where the research is carried out. The third is to support the improvement of specific types of infrastructure, i.e., bioinformatics and biorepository capacity, which are needed to do genomics-based and environmental research. To achieve these objectives, the H3Africa program at NIH will comprise the following: Infrastructure improvement will be addressed by support for an H3Africa Bioinformatics Network (see companion FOA, RFA-RM-11-010) and for up to four planning grants for biorepositories in Africa (see companion FOA, RFA-RM-11-011). It is anticipated that one or more full-scale H3Africa Biorepositories will be established in Africa after the planning grant/feasibility phase. A companion FOA to this document (RFA-RM-11-009), Human Heredity and Health in Africa (H3Africa): Research Projects calls for genomic/genetic research applications from individual investigators who wish to add a genomics component to an existing disease-based research effort. The current FOA calls for applications for the H3Africa Collaborative Centers, which should include opportunities for genomics/genetics /environmental research, research training, administrative training, and career support in a multi-institution collaboration . Finally, there will be a small grant program, that will be funded in FY13, to support research on the societal implications of genomics in Africa. All awards under the NIH H3Africa program will be made to African Institutions and the majority of the awarded funds must be spent in Africa. All awardees will participate in the H3Africa Consortium to further enhance the collaborative nature of this Initiative.

H3Africa is funded, in part, through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Research Objectives:

A. Scientific scope

The objective of this FOA is to solicit applications to establish H3Africa Collaborative Centers (H3ACC) to implement research projects that will apply genomic approaches to understand the genetic and environmental contributors to chronic and infectious diseases and health in Africa. Each H3ACC will be composed of multiple projects that collaborate to provide the complete capacity needed to carry out a genomics-based research project on a disease or condition important to Africa. The Centers will have a strong training and career development component and clear organizational and management structures.

The scientific focus of applications responsive to this FOA will broadly be within the scope of human genetic/environmental contributors to disease and other health-related traits in Africa. The following list provides examples of the types of topics that may be addressed. It is important to note, however, that this list is meant only to provide guidance; it is not exhaustive and appropriate topics are not limited to the examples given here.

• The genetic/environmental contributors to non-communicable disease in Africa. The burden of chronic diseases in Africa has been difficult to measure because of the absence of a coordinated process to estimate disease prevalence. However, a small set of prospective studies and hospital experiences have identified the increasingly important impact of chronic disease. Examples include a substantial burden from hypertension, a high mortality rate from stroke, a rapidly growing threat from diabetes, and an increasing recognition of the prevalence of mental illnesses. Some clinical and epidemiologic research on such chronic conditions has been conducted in several sites on the continent, and clinical expertise can be found in many hospitals and tertiary care settings related to these conditions. A small number of linkage, candidate gene, and genome-wide association studies (GWAS) have been completed and have been able to identify potential new loci involved in disease, as well as replicate findings from other studies. An appropriate H3Africa project might involve collection of new or existing samples from one or more populations of interest from specific site(s). The individuals from whom samples are collected should be well-phenotyped to ensure that the disease being studied has been properly diagnosed. Samples may be assayed by, for example, genotyping, exome or whole genome sequencing, and/or functional genomics methods to fully elucidate the genetic underpinnings of the disease or trait of interest. Analysis of exposure data on these individuals could provide evidence about the environmental factors that, in conjunction with the genetic determinants, could help explain the etiology of the disease under investigation.
• The genetic/environmental contributors to communicable disease in Africa. Infectious diseases, including HIV/AIDS, malaria, tuberculosis, leishmaniasis, trypanosomiasis, schistosomiasis, as well as many others, have historically been a major health problem in Africa. A variety of genetic and environmental factors contribute to developing, treating and preventing infectious diseases and their impact. Significant attention and considerable funding has been given to the study of communicable diseases, and excellent research facilities for studying them are found throughout Africa. One of the important aspects of the widespread nature of infectious diseases and the high rates of infection in populations living in similar environmental conditions is the considerable inter-individual phenotypic variability in susceptibility and response to infection, which can range from asymptomatic to death. Contemporary genomic approaches can help to understand the role that host genetics plays in these diseases. Similarly, additional genomic analysis and studies of the genetics of the parasites and vectors involved in the diseases are needed. HIV/AIDS and malaria are among the most well-studied communicable diseases in Africa. While NIH will consider study of the host factors involved in susceptibility to HIV infection and diseases that are co-morbid with HIV/AIDS (see below) as being responsive, studies of other infectious diseases are encouraged.
• The contribution of the human microbiome to health and disease in Africa. The field of metagenomics has been enabled by recent advances in sequencing and other technologies, and studies of the role(s) of the human microbiome in health and disease have burgeoned. Changes in the microbiome at particular body sites have been correlated with the onset or progression of several diseases, such as Crohn’s disease, psoraisis and bacterial vaginosis. Most microbiome studies have been done outside of Africa, but given the expectation that microbiome composition is highly dependent on many environmental factors, including geographical location, diet, socio-economic status, as well as host genetics, the relevance of the results of those studies to health and disease in Africa cannot be assumed. As an individual’s microbiome is expected to make a significant contribution to health status, studies of the role of the microbiome in diseases of African interest, and comparative analyses of microbiomes from healthy cohorts, would be appropriate H3Africa research projects.
• Mendelian diseases in Africa. Local founder effects and the cultural practice of consanguineous marriages in many African communities have resulted in the increased prevalence of monogenic traits across the continent. Recent studies have demonstrated that exome sequencing of a limited number of individuals can be used effectively to identify causative mutations in several Mendelian diseases. An analysis of individuals affected by Mendelian diseases to identify causative mutations and modifier genes in African populations would be appropriate H3Africa research projects.
• Pharmacogenomics: Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to adverse drug reactions (ADRs). African populations have been underrepresented in pharmacogenomics research. Yet these populations show the highest levels of genetic diversity among human populations. Pharmacogenomics can be applied to numerous treatments of illnesses that plague the African continent, for example, identification of the genetic variant(s) involved in inter-individual variability in the response to chemotherapy drugs used in cancer treatment, drugs used for the treatment of HIV, malaria,and other infectious diseases, as well as pain medication. Analysis of pharmacogenetic effects in Africans would be an appropriate H3Africa research project.

While applications submitted in response to this FOA may propose research in any disease or health area that falls within the broad areas of genetic/environmental contributors to disease or health research, there are also specific areas of interest to the NIH components that are participating in H3Africa. These include:

• AIDS and co-morbidities. Research examining the genetic and genomic basis of HIV/AIDS disease and its co-morbidities including, but not limited to, host immune response to HIV infection; interaction of HIV with the host immune system; genomics in the context of HIV vaccine and microbicide development; host factors involved in co-infection, including tuberculosis, hepatitis C and hepatitis B in the context of HIV infection; host factors involved in AIDS-defining and non-AIDS defining malignancies in HIV-infected individuals; and host factors involved in complications associated with long-term HIV disease and antiretroviral therapy (ART), including metabolic disorders, cardiovascular disease, conditions associated with aging, and neurologic and neurocognitive disorders.

Neurological disorders and stroke: Research in neurological projects that address the H3 goals are of interest. Study designs may include a broad range of disciplines, such as molecular genetics, pharmacogenomics, epidemiology, stigma research, and intervention research. Quality phenotyping is essential for genetic research; therefore, collection and analysis of genetic material from individuals participating in well characterized, neurological-based cohorts materials is of high interest, particularly in the the areas of stroke and stroke risk factors, epilepsy, and susceptibility to peripheral neuropathy due to infection or inflammation, as well as other neurological diseases and disorders. Applications that enhance the NIH-funded Medical Education Partnership Initiative (MEPI) training experience are encouraged (http://www.fic.nih.gov/Grants/Search/Pages/Awards-Program-MEPI.aspx). Applications that use technologies such as mobile technologies that enhance health, knowledge, or care delivery of neurological disorders are also of interest.

• Genetic and genomic basis of HIV/AIDS disease, abuse of licit or illicit substances (including alcohol, tobacco, cannabis, stimulants, opiates), and related co-infections or co-morbidities: Topics include, but are not limited to studies of the host and viral determinants of immune responses to HIV infection in substance users, particularly related to specific disease phenotypes; the factors related to immune recovery following antiretroviral treatment in the context of substance use; determinants of susceptibility to HIV infection among substance users; complications associated with long-term HIV disease and substance use, such as tuberculosis, HIV/HCV-associated liver disease, cardiovascular disease, metabolic disorders, and neurologic and neurocognitive disorders; and viral evolution in association with injection or non-injection substance use.

B. Implementation of the objectives of H3Africa.

As noted in the Background section, there are several specific objectives that the H3Africa Program is trying to achieve. Applications submitted in response to this FOA must address the following:

• Interaction with other programs. The H3Africa requires the collaborative centers to form partnerships in Africa with institutions that have ongoing studies and offer infrastructure in the research focus area but are not currently conducting genomics and environmental research. The objective is to rapidly expand the cadre of skilled genomicists throughout the continent through collaborations with expert genomicists, through career building within the Centers, and via training opportunities offered by the Centers. This is in addition to the expected training of new students, postdocs, technical support staff and others within the Collaborative Centers. Collaborations could leverage existing NIH and WT initiatives in Africa http://www.h3africa.org/resources.cfm, in addition to other funded activities supported by other U.S. government (USG) organizations such as the CDC, DOD, HRSA, USAID or non-USG entities such as the Doris Duke Charitable Foundation and the Bill & Melinda Gates Foundation. The Common Fund joined forces with PEPFAR to fund one such initiative in 2010, called the Medical Education Partnership Initiative (http://www.fic.nih.gov/Grants/Search/Pages/Awards-Program-MEPI.aspx), which is building capacity in medical education, clinical, and research capacity in Sub-Saharan Africa, and is already establishing infrastructure in various areas including computational hardware and connectivity, clinical training including in rural settings, research administration training, and research ethics training.
• Research plan. The application should describe a well-conceived plan for the investigation of the genomic, and at the applicant’s discretion the environmental, contributor(s) to a disease or other health-related condition. The applicant should provide a compelling justification for the choice of the condition to be studied and should clearly state how the research proposed will lead to an improved understanding of its genetic and environmental origin(s). The application should provide a description of the health impact of the condition in Africa, and the relationship (if any) to the condition in other parts of the world. The applicant should present a well-considered plan for accomplishing the goals of the research applications for both the overall collaborative center and for each of the collaborating components. The plan for the overall center should discuss the types of data that will be analyzed and how those data will be obtained (see below). The plans for the collaborating components should describe the specific contribution that each component will make to the identification and acquisition of the samples to be analyzed, the generation of the data, and the management and analysis of the data.

If the data are to be generated by the center itself, the applicant’s experience with the necessary technologies, the costs of generating the data, and the anticipated uses should be addressed. The availability of samples and supplies should be discussed, as should any issues of long-term maintenance and servicing of the necessary equipment.

Alternatively, the applicant may choose to send the samples elsewhere for data generation, for example to other research centers or to service providers. Such an approach could be taken, for example, for genotyping, microarray analysis or sequencing. In either case, the data generator may be in Africa or overseas. In describing this approach, the applicant should describe how the samples will be prepared for shipment to the data generator, the type of data expected, and how the data will be returned to the center for analysis.

The applicant should describe how the resultant data, whether produced in-house or obtained externally, will be analyzed, including a discussion of the applicant’s experience with the relevant analytical technologies and methods.

Sample collection and Human Subjects Issues. The research plan must include a detailed plan for sample acquisition (where applicable), storage, preparation of material needed etc. In particular, investigators are urged to obtain consent for the wide sharing of samples and data; justification should be provided if samples and data will not be shared or only shared in a limited manner. A document entitled "Essential Elements of Informed Consent for H3Africa Research Projects" may be helpful to applicants in writing their informed consent documents; this can be found at http://www.h3africa.org/informedConsent.cfm. A timeline for developing and implementing an informed consent process, including obtaining IRB approval, must be included in the application.

H3Africa anticipates establishing a biorepository in Africa starting in 2014. All samples (blood, DNA or cell lines) are expected to be deposited in the H3Africa Biorepository where they can be distributed and shared for further research consistent with achieving the goals of this funding initiative. Sample deposition must occur expeditiously, no later than the date of the first publication that describes the samples or by the end of the project, whichever comes first. A statement of commitment from the applicant institution to send samples to the H3Africa Biorepository must be included in the application, consistent with achieving the goals of the H3Africa initiative. This should include a description of the host country’s policies for sending samples out of the country.

Collaboration. Most of the collaborations in which African biomedical research scientists have been involved have been with scientists from abroad, rather than with other Africans. One of the goals of the H3Africa Initiative is to foster collaborations between and among investigators within Africa in order to build a larger African scientific community that will lead to more training opportunities and cutting-edge science on the continent. Such collaborations will also contribute to sustainability of African genomics programs. Therefore, applications submitted in response to this FOA will be required to be structured around significant collaborations with scientists at other institutions within the applicant’s home country or with scientists in other African counties. One example of an acceptable collaboration would be one in which each aspect of the overall research program, such as sample acquisition, phenotyping, genomic data generation, data analysis, is done by a separate component. Another example would be one in which a full genomic analysis is done at each collaborating component on a different sample population and the results combined for a comparative analysis. These examples are only intended to be illustrative; the organization of the collaborative activities will be determined by the investigators involved and the applicants should propose the set of collaborations that would best achieve the proposed research objectives. While international collaborations with scientists outside of Africa may be included, the majority of the collaborative activity should be within Africa.

All applications must include a description of the overall set of proposed collaborations, how each collaborative component will contribute to the functioning of the Collaborative Center, how the collaborating groups will communicate, and how the overall Collaborative Center will be managed with collaborations that are not on site. If appropriate, one of the collaborating components can be a management core.

Training and Career Building. Establishing the next generation of African researchers to take advantage of genomic approaches to health research is a critical objective of the H3Africa program. Therefore, the applications must include a component which may address either training, or career development, or both.

• Training. In this FOA, training is meant to include the education in science and research techniques of graduate students at both the MS and PhD levels, of post-doctoral researchers, and of faculty through support for sabbaticals. It also includes technical training of laboratory staff. Other types of training will be considered if appropriately justified.Applicants will have wide latitude in designing the training programs, which may be directed at as many of those levels as desired and for any period of time. While it is expected that the majority of training will take place in African institutions, training opportunities abroad can also be included; in that case a plan for the return of the trainees back to Africa is required. The training program may include both coursework, laboratory experience, and mentoring. The applicant s training experience should be adequately presented.
• Career development. Fostering the careers of recently trained doctoral-level investigators by recruiting or engaging them in the research programs as leaders of components is another valuable contribution that the Collaborative Centers can make to establishing the next generation of African researchers, and applicants are strongly encouraged to include a career development component in the application. Start-up funds for new investigators can be requested to enable them to establish their own laboratories.

A well thought-out plan for the training and career building program, its applicability to the research and its long term contributions to the goals of H3Africa should be included. Long-term sustainability and institutional/governmental commitments to the training program and the independent career positions established through the Centers should also be discussed. Applicants should note that the Medical Education Partnership Initiative (MEPI) is a sister initiative to H3Africa within the Common Fund's overall Global Health Program. H3Africa applicants are encouraged to collaborate with MEPI grantees as part of their training program where possible, in order to take advantage of the training infrastructure and opportunities available through MEPI.

Bioinformatics. The bioinformatics capacity of the Collaborative Center should be clearly described, both at the level of the overall center and at the level of each of the collaborating components. Issues of data acquisition, data management, data storage, and analytical capability should be addressed. The bioinformatics tools that will be used for each of those functions, and the applicant’s experience should be described in the application. These bioinformatics activities may be embedded within the individual research components or may appear as a separate bioinformatics core in the Center. Additionally, a bioinformatics research component, for example new computational tool development, may be included within the research application as one of the collaborative aspects.

Please note the H3Africa Program will fund a separate H3Africa Bioinformatics Network (see companion FOA, RFA-RM-11-010) to provide connectivity among the H3Africa participants, and eventually beyond H3Africa. The H3Africa Bioinformatics Network will also have the ability to develop new bioinformatics tools for genomics research in Africa. The Collaborative Centers and any other H3Africa-funded activity will be required to interact with H3Africa Bioinformatics Network. Therefore, applicants for a Collaborative Center award must include a statement from the applicant institution committing it to collaborating and sharing data with the H3Africa Bioinformatics Network consistent with achieving the goals of H3Africa.

• Infrastructure. To the extent possible, the Collaborative Centers are expected to utilize existing infrastructure in the research institutions where the studies will be carried out. A description of existing institutional infrastructure must be provided in the Resources section of the grant application. This section should be detailed and well documented. Additional infrastructure components may be requested in the application.
• Equipment. In the first year, up to $250,000 total costs for equipment may be requested beyond the $920,000 direct cost cap for the Collaborative Center budget (see Section II, Award Budget, below). The equipment must be used for the research project and must be well justified. However, these funds will be restricted for purchase of equipment only, and cannot be used to augment the research budget. Any request for equipment beyond this $250,000 limit will have to be included within the $920,000 cap and will, therefore, reduce the amount of operating research funds. The requests for equipment within the $250,000 limit for restricted equipment funds should be made separately from additional equipment requests made from research project funds.
• International Extramural Associates Research Development (IEARD) component.

A Collaborative Center and its host institution must have an effective administrative infrastructure. It must also have the ability to provide effective administrative management and careful oversight of the award and, more generally, of the conduct and support of research. Funds (up to $35,000 direct costs) must be requested within the Collaborative Center application to support a program of training in the NIH grant process. The funds will be used for a training program that will be administered in conjunction with the National Institute of Child Health and Development's International Extramural Associates Research Development Award program (see http://nichd.nih.gov/about/org/dsp). The training component will support the following for a single individual from the applicant institution: an initial orientation implemented through a distance learning component, and a two-week training curriculum on-site at the NIH (in Bethesda, MD, USA) for a single research administrator to learn about grants management, NIH policies and procedures, fiscal accountability and research. Upon return to his or her home institution, that individual will be responsible for designing and implementing an Infrastructure Development Plan. The institution will be equally responsible for approving and carrying out the plan and for providing sustainable support for it as an ongoing institutional component. The research administrator will use the funds set aside for this purpose from the Collaborative Center grant during the period of the grant to improve and reinforce the institution’s research capacity and research administration infrastructure (through the Office of Research or Office of Sponsored Projects), as outlined in the final, approved version of the Infrastructure Development Plan.

If the institution’s administrative staff have already received such training or believe they have enough experience that they do not need this initial training, the application should provide information about the staff’s level of experience and previous training received, and should propose an administrative training program that is appropriate to their level of experience. See Additional Instructions below for information about what must be included in the IEARD program request.

• Societal Implications Research: Applicants may be interested in including studies of the societal implications, including ethical and legal issues, of genomics-based research in Africa into their Collaborative Center application. Support for such research may be requested as an integral part of one of the collaborative research projects proposed within the center or as a separate collaborative project within the Center. As noted above, H3AFrica will also sponsor a small grant program to fund applications in this area in 2013.
• Sustainability: One of the major goals of the H3Africa program is to enable African scientists to demonstrate their world-class skills through the establishment of cutting-edge research programs that will lead to more publications and other evidence of productivity, thereby increasing their opportunities for future funding through normal competitive grant processes, as well as through increased investment in research by national governments and private sources. Applicants should discuss the issue of future sustainability of their research programs beyond the H3Africa program and how the Collaborative Center activity will contribute to the on-going stability of the research efforts of all of the participants in the Center. This section of the application should refer to the letters of Institutional and National commitments (see below) to provide an overview of the long term prospects for sustained research by the Center and each of its components.
• Data Sharing and Release plan: A plan for data and resource sharing and release is expected for all NIH applications (http://grants.nih.gov/grants/policy/data_sharing/). Applicants are expected to provide a well thought-out plan for widely sharing data and resources generated by Collaborative Center to further the H3Africa goal of encouraging more research by Africans on health and disease in Africa. An application must have an acceptable Data and Resource Sharing and Release plan before it can be funded. After the awards are made, the H3Africa Consortium (see below) will develop a unified plan for data and resource release, and the application must include a statement that the investigators in the H3ACC will abide by the Consortium’s data and resource policy. Examples of current data release guidelines for NIH programs can be found at: http://www.h3africa.org/dataReleasePolicy.cfm
• H3Africa Consortium Meetings: The NIH and the Wellcome Trust plan to hold two H3Africa Consortium meetings per year, and applicants should request funds to travel to these meetings in their application. Most of the meetings will be held in Africa. However, in the first year, one of the Consortium meetings will be held in London, UK, and in year three, one will be held in Bethesda, MD. It is expected that each research project and administrative core (if part of the U54 structure) will bring 1 to 2 people to the meeting. For the meetings in London and Bethesda, each research project should be represented by at least the PD/PI and two trainees. Appropriate travel funds for these meetings must be requested in the application.
• Monitoring and Evaluation Plan: Applications must contain a plan for how the funds and supported activities will be monitored and evaluated. The plan should discuss how the project will be assessed and how the applicant will define, identify, and determine impact. The plan should also discuss how any necessary modifications indicated as a result of monitoring and evaluation activities will be effected. To facilitate monitoring and evaluation, applications should include a well-defined set of yearly milestones for the proposed research and training activities. The milestones will be negotiated and finalized at the time of award, and will then be included in the Terms and Conditions of the award. The milestones will be subject to change only with the NIH Program Director’s agreement, but will be reconsidered on an annual basis to account for the Center’s experience and progress. An example of the level of detail and specificity needed for the milestones can be found in an example set of acceptable milestones from past genomics projects, posted at http://www.h3africa.org/genomicsProjectMilestones.cfm.
• Institutional and National Commitments: Applications should include letters from the appropriate institutional official (University or Medical School President, Dean or Director, or the head research administrator or equivalent) from all collaborating institutions substantiating the institution’s commitment to the proposed research. The institution should state its commitment to overcoming any administrative obstacles to the implementation of the proposal, such as accommodation for participation by multiple Schools at the university or collaboration with other institutions within or outside of the applicant s country. Appropriate institutional commitment to the program includes the provision of adequate staff, facilities, and resources that can contribute to the planned program. As described in preceding sections, the letter should address institutional commitment to any new faculty whose labs are established within the Center. It should also address commitment to collaborating and sharing data with the H3Africa Bioinformatics Network. The letter should also briefly discuss the institution's plans for sustaining an active program of scientific research.

As the programmatic activities of this initiative will support national and international collaborations, letters of support from the related national ministries such as the Ministry of Science, Ministry of Health and/or Ministry of Education for each African country with a programmatic component will be required. The letter should briefly describe the national policy concerning the development of a national scientific research program and how the country is addressing the target that the African Union set in 2006 for each nation to spend 1% of its gross domestic product (GDP) on research and development (R&D). It is highly recommended that these letters of support be included with the application. If these are submitted later, this could impact and delay the review of the application. An award will not be made without receipt of these letters of support.

In Summary: This FOA calls for applications for H3Africa Collaborative Centers to carry out the research goals of H3Africa, which include:

• establishment of viable, productive, and eventually sustainable, African research programs for the study of the genetic and environmental contributors to disease and health,
• improving the research environment by leveraging current expertise and existing infrastructure with new investments, and
• training and career development
• exploration of the social implications of genomic research in Africa (optional in the Collaborative Centers).

The scientific scope of the H3Africa Collaborative Centers is broad, and may address:

• the genetic/environmental contributors to non-communicable disease in Africa,
• the genetic/environmental contributors to communicable disease in Africa,
• the human microbiome in Africans and its contribution to health and disease,
• Mendelian diseases,
• Pharmacogenomics,
• Other

It is strongly suggested that applications will address the following:

• Research plan, including the qualifications of the PD/PI(s) of the overall Collaborative Center and of each of the collaborating components.
• Sample collection and human subjects issues
• Collaboration plans
• Training and career development
• Bioinformatics, including connection to the H3Africa Bioinformatics Network
• Available infrastructure,
• Equipment within the amount of restricted funds available, and in excess of that amount (if necessary),
• Research administrator development
• Data sharing and release,
• Monitoring and evaluation,
• Institutional commitment,
• National plans for science

Funding Instrument	Cooperative Agreement
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	This initiative is supported by NIH Common Fund, Institute(s) and Center(s) and Offices of the NIH who have signed on to support the H3Africa initiative. The amount of funding and the number of awards will rely upon the outcome of peer review, the interests of the NIH institutes, and the availability of funds. The total amount of funds available for these awards is approximately $3.75 million per year for FY12-16, contingent upon receiving scientifically meritorious applications. Up to 3 awards are anticipated from this solicitation.
Award Budget	Applications are limited to $920,000 direct costs which includes salaries, supplies, training, equipment, travel, and other allowed expenses for research grants. In order to address H3Africa's goals to build infrastructure each applicant may request up to an additonal $250,000 for equipment. The request for equipment must be very well justified. In subsequent years the research plan budget may not exceed $920,000 direct cots. $35,000 direct costs/year must also be set aside for participation in the International Extramural Administrative Research Development Program component (see above) under Implementation of H3Africa Objectives section..
Award Project Period	Scope of the proposed project should determine the project period. The maximum period is 5 years.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Specifically:

• African institutions are eligible for the awards:
• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

Common Fund/Roadmap text, Collaborative Research, or Projects Greater than 5 years Duration: See instructional documents in the NIH Guide Publishing System for the text to insert.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

The PD/PI should be an established leader in the academic and scientific area in which the application is targeted and capable of providing administrative, clinical, and scientific leadership to the development and implementation of the proposed program.

More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application for projects that require a team science approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH electronic Research Administration (eRA) Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed research
• Name, address, and telephone number of the PD(s)/PI(s)
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

The letter of intent should be sent to:

Jane L. Peterson, Ph.D.
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9305
Bethesda, MD 20892-9305
Phone: 301 496 7531
Fax: 301 480 2770
Email: Jane_Peterson@nih.gov

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9305
Rockville, MD 20852

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Dr. Rudy Pozzatti, PhD
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9306
Bethesda, MD 20892-9306
Phone: 301-402-0838
Fax: 301 435 1580
Email: rudy.pozzatti@nih.hhs.gov

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9306
Rockville, MD 20852

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:

The research Strategy section for each component of the scientific of the collaborative center is limited to 12 pages in length. If there is an administrave core, it is limited to 6 pages in length.

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

The application must include a detailed research plan that is responsive to the objectives of the H3Africa program, as set forth in this FOA (see Research Objectives). An H3Africa Collaborative Center must comprise at least three collaborating components that together address one or more of research areas, examples of which are given in the Research Scope section of this FOA. At least one of the collaborating components must be outside of the applicant institution; bi- or multi-national collaborations are encouraged.

• An Overall Research Strategy should describe the scientific objectives of the H3Africa Collaborative Center, the question(s) that will be studied, the methods and technologies that will be used, the contributions of each of the collaborating components, and the way in which the collaborations will synergize. The Collaborative Center’s approach to meeting its bioinformatics needs, its approach to obtaining informed consent and other aspects of the protection of research participants (if applicable), and its approach to issues concerning research animal welfare should all be discussed in this section. The Overall Research Strategy is limited to 12 pages.
• Research strategies for each of the collaborating components should describe in more detail the specific contribution that the component will make to the overall success of the Collaborative Center, the methods and technologies that will be used, the investigator(s)’s experience with conducting research and employing the appropriate methods and technologies, the approaches to meeting the bioinformatics needs of the component, the component’s approach to informed consent and protection of research subjects (if applicable) and research animal welfare (if appropriate), any other issues that are specific to the individual component. This section should also describe the way in which the component will interact with the other components of the Collaborative Center. The research strategy for each component will be limited to 12 pages.
• Training Program. A description of the Collaborative Center's training and career development objectives and how it will meet them should be provided as a separate section, limited to 12 pages in length. The training and career development activities may be presented separately within the 12-page limit. The description should address the objectives of the Collaborative Center s training and career development activities; how the trainees and new investigators will be identified; the specific training and career development activities that will be supported within the Collaborative Center, including mentoring activities; where the training will take place; opportunities for cross-training within the Center’s collaborating components (as applicable); the role of training opportunities outside of the Collaborative Center; and plans for monitoring the progress of individual trainees and new investigators.
• Administration and Management. The organizational structure of the Collaborating Center, and the plans for administering, managing, tracking, and coordinating the activities of the Center and its individual components should be described in a separate section, limited to 12 pages in length. The Collaborative Center’s plans for data release, resource release, intellectual property disposition, and monitoring and evaluation should be included in this section. If desired, these activities can be included in a separate Administrative Core.

The Adminstration and Management section should also include a description of the applicant institution's current capacity for administration of research grants, including information about the placement of the designated research administrative infrastructure (e.g., Office of Research, Office of Sponsored Projects) within the institution and its line of authority, the institutional provision of resources such as office space, administrator salary, office equipment and other in-kind activities, and the applicant institution's plans to support and sustain the research office. The application should also describe any plans the institution has for further development of its research administration program.

The H3Africa Collaborative Center award will include $35,000 in funds per year to support such further development at the applicant institution. It is expected that by the end of year -01 of the Collaborative Center award, one or more research administrators will have received training equivalent to that provided by the NICHD International Extramural Research Administration Development Award (IEARDA) program. The purpose of the IEARDA program is to increase the knowledge and/or experience of research administrators with funding opportunities, grant applications, research program and project oversight, data management, fiscal accountability, and scientific reporting requirements of the NIH and other international research funding agencies, all of which will be important in the adminstration of the Collaborative Center award. If at least one individual at the applicant institution who will have significant responsibility for the management of the Collaborative Center award has participated in the NICHD program, the application should document that and then describe the applicant institution's plans to use the specified funds to enhance and further strengthen its research administration activities. If no individual at the applicant institution has yet received such training, the specified funds should be used to support an individual to participate in this program at the earliest possible offering after an award is made (the NICHD has agreed to accept one person from each awarded Collaborative Center into its training program). NICHD will review the qualification of the person nominated before accepting him or her in the IEARDA program The application should thus identify the person or persons who will be responsible for administering the Collaborative Center award and a Biosketch should be provided for each. The application should also include a brief, one to two page, description of the Center's and applicant institution's plans for the administration of the award (equivalent to the Institutional Development Plan of the IEARDA program). Finally, the application should include a statement of support from the applicant institution that provides approval of the nominee’s IEARD training periods at home through the distance learning component and at the NIH for the NIH residency, and provides the release time for these periods and any financial support needed for training. This statement of institutional support may be included in the required Letter of Institutional Support described in the Implementation of the Objectives of H3Africa section above. More about this program can be found at http://www.H3Africa.org/IAERDinfo.cfm.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS398 Application Guide, with the following modifications:

• H3Africa resource and data sharing plans will be agreed to by the entire network once all the applications are funded. However, applicants must provide a plan in the application that must be approved by H3Africa program staff before the application can be funded, consistent with the goals of the H3Africa initiative.
• All applications, regardless of the amount of direct costs requested for any one year, should address a data sharing plan

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide.

Foreign (non-US) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS398 Application Guide.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

The H3Africa staff will host a meeting for applicants to discuss the NIH Funding Opportunity Announcements (FOAs) regarding H3Africa. The FOAs call for applications for H3Africa research projects, bioinformatics networks, collaborative research centers and Biorepository planning grants. The meeting will be held on the 21st and 22nd of September 2011 at the Windsor Golf Hotel and Country Club in Nairobi, Kenya.

On the 21st of September staff will discuss each FOA, be available to answer questions and hold proposal writing and grants management workshops specific to the NIH application process. On the evening of the 21st and the day of the 22nd of September NIH staff will be available to meet with applicants individually with the understanding that the general questions they ask and answers given by staff will be posted on a website.

Applicants interested in meeting separately with staff should schedule an appointment by sending an email to H3Africa_meeting@mail.nih.gov . A teleconference link will be provided for individuals unable to attend the first day of the conference. The agenda, information regarding accommodation and the details of the teleconference can be found here. While registration for the meeting, except for the teleconference, is not required please inform H3Africa staff of your intent to attend by sending an email to H3Africa_meeting@nih.mail.gov . This will enable NIH to provide you with any updates or additional logistics about the meeting.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the Collaborative Center (CC) to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the center proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a Collaborative Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the propsed Collaborative Center address an important problem or a critical barrier to progress in the field? If the aims of the Colllaborative Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? How will the goals of the proposed Collaborative Center address the goals of H3Africa? How will collaborations with other institutions both within and outside the country contribute to the success and sustainability of the program?

Investigator(s)

Are the PD/PIs, collaborators, and other researchers well suited to the Collaborative Center? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? How does the program promote and support innovation that will strengthen and sustain genomics research in Africa?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Collaborative Center? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

If the Collaborative Center involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed? Will the training program proposed be effective in addressing the training goals of H3Africa? Will the Center support the career building objectives of H3Africa? Are the bioinformatics data handling and analysis plans adequate to address the needs of the Center? Is the proposed collaborative nature of the Center conducive to achieve the Center's goals? Are the evaluation plans, milestones and timelines proposed appropriate and adequate for the project? Has the issue of future sustainability been adequately addressed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Does the Center take advantage of resources available at the collaborating institutions? Does the proposal identify and plan to take advantage of other resources at the participants' institutions, countries or other countries where necessary?

As applicable for the Collaborative Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Center as an Integrated Effort Overall Impact

• Are the efforts at coordination, interrelationships, cohesiveness, and synergy among the Collaborative Center's components adequate as they relate to the common theme of the center?
• Does the application provide adequate evidence of the advantages of conducting the proposed research as a collaborative program rather than through separate research efforts? Will the research efforts taken together have more impact on the field than each separate project conducted in isolation? Will the research proposed in individual projects be enhanced by being part of the Collaborative Center?
• Are there adequate mechanisms proposed for regular communication and coordination among investigators in the Collaborative Center?
• Are adequate administrative structures in place for the day-to-day management of the center, including arrangements for internal quality control of ongoing research?

Sustainability

Is the Center's plan for sustainability feasible? Will the Center and/or its components be well-positioned to apply for continued funding at the end of the project period?

Do the letters of Institutional and National commitment suggest that the environment is conducive to a sustained research enterprise?

Do the collaborations among the institutions suggest viable long-term partnerships?

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed center involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact/priority score.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan: Does the proposed data release plan constitute a good basis for negotiating a final data release plan? Does the applicant indicate a willingness to accept the H3Africa's consensus Data Release policy?; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Human Genome Research Institute , in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review), will be discussed and assigned an overall impact/priority score.
• Will Receive a second level of review by the appropriate National Advisory Council
• Will receive a written critique.

Applications will be assigned to the appropriate NIH Institute or Center and will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate National Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• How well the application addresses the goals of H3Africa
• Overall program balance in the H3Africa program

Appeals of initial peer review will not be accepted for applications submitted to this FOA.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipient’s activities by involvement in and otherwise working jointly with the award recipient in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardee(s) for the project as a whole, although specific tasks and activities may be shared among the awardee(s) and the NIH as defined below.

Definitions

Steering Committee (SC):

The Steering Committee is the primary governing body of the Consortium. PI(s)/PD(s) of the cooperative agreements, and NIH Program Directors serve on the committee. See further details about the Steering Committee under "Joint Responsibilities".

Panel of Scientific Consultants (PSC)

The PSC will be composed of four to six senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the H3Africa Consortium. The PSC will be responsible for monitoring and assessing the progress of the H3Africa Consortium. See more about the PSC below under this topic .

The PD(s)/PI(s) will have the primary responsibility for:

• All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms or by action of the Steering Committee.
• Awardees agree to the governance of the H3Africa Consortium rough the Steering Committee and recommendations from the Panel of Scientific Consultants.
• Awardee(s) will agree to accept close coordination, cooperation, and participation of NIH H3Africa staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."
• Awardee(s) will provide goals and progress toward those goals at regular intervals as requested by NIH H3Africa staff and will ensure that the data produced meets the quality standards agreed to at the beginning of the project by the H3Africa Consortium;
• Awardee(s) will ensure that the data are deposited in the appropriate public database (e.g., GenBank or other, as specified by NIH H3Africa program staff), that resources developed as part of this project are made publicly available according to H3Africa Consortium policies, and that results are published in a timely manner;
• Awardee(s) will adhere to the H3Africa policies regarding intellectual property, data release and other policies that might be established during the course of this activity consistent with applicable NIH policies, laws, and regulations;

Awardee(s) will integrate with and connect to the H3Africa Bioinformatics Network (see FOA RFA-RM-11-010 and deposit samples in the H3Africa Biorepository that is anticipated to be [t1] established;

• Awardee(s) will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• One H3Africa Project Scientist from each participating Institute will serve on the Steering Committee and have one vote; the number of NIH votes may not exceed the number of PI/PD votes on the SC. They and other NIH H3Africa project team scientists may serve on sub-committees or working groups, e.g., data sharing, data release, quality control, core establishment, as appropriate. The NIH H3Africa Project Scientists may work with awardees on issues coming before the Steering Committee and other sub-committees and working groups.
• The Project Scientists will participate (with the other Steering Committee members) in the group process of deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted.
• The Project Scientists will negotiate goals with the awardees as necessary; will serve as liaison between the awardees and the Panel of Scientific Consultants, the appropriate NIH Institute and Center National Advisory Councils, the H3Africa Working Group made up of staff that collectively manage the program and the larger international scientific community; attend all Steering Committee meetings as voting members as described above; and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• The Project Scientists will periodically report progress to the Director, Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), of which the Office of Strategic Coordination that manages the NIH Common Fund is a part of as well as OAR, and to the Directors NHGRI, FIC, NINDS, NIDA, and NICHD.
• The Office of Strategic Coordination (OSC), NHGRI, NIDA, NINDS, NICHD, and OAR reserve the right to withhold funding or curtail the study (or an individual award) in the event of (a) substantive changes in, or failure to make sufficient progress, toward the agreed-upon work scope with which the OSC, NHGRI, NIDA, NINDS, NICHD, and OAR cannot concur, (b) human subject ethical issues that may dictate a premature termination.
• Support or other involvement of industry or any other third party in the study -- e.g., participation by the third party; involvement of study resources or citing the name of the study or NIH support; or special access to study results, data, findings or resources -- may be advantageous and appropriate. However, except for licensing of patents or copyrights, support or involvement of any third party will occur only following notification of and concurrence by NIH.
• Additionally, an agency program official or NIH program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as an NIH Project Scientist.

Areas of Joint Responsibility include:

Steering Committee participation. A Steering Committee (H3ASC)will serve as the main governing board of the H3Africa Consortium. The Steering Committee membership will include the NIH Project Scientist(s) and the P.I. of each awarded cooperative agreement. The Steering Committee Chair will not be an NIH staff member but will be appointed by NIH H3Africa staff. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. Because the Consortium will include investigators funded as a result of this FOA and of other H3Africa FOAs, it is possible that NIH H3Africa staff will create appropriate subcommittees to handle interests that may be specific to a set of awardees funded as a result of a specific FOA.

The Steering Committee will:

• Discuss progress in meeting the goals of various H3Africa projects;
• Facilitate coordination and synergy across the entire H3Africa program;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the Consortium, for example for data quality measures and assessment, conventions for data deposition;
• Schedule the time for, and prepare concise (3 to 4 pages) summaries of, the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting. The SC will meet twice a year with intermittent conference calls.

Each full member (limited to one person per awarded center, in the case of multiple PIs per center) will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

The Panel of Scientific Consultants (PSC):

The PSC will make regular assessments and provide recommendations to the Directors of NIH funding components about progress of the H3Africa components toward the goals of the H3Africa program and about continued support of the components of the H3Africa Consortium.

• The PSC will meet at least once a year. During part of this meeting, there will be a joint meeting with the H3Africa Steering Committee to allow the PSC members to interact directly with the awardees.
• Annually, the PSCs will provide assessments regarding the progress of the H3Africa Consortium and of the individual components and, as necessary, will present recommendations regarding any changes that may be necessary in the H3AFrica program to the Directors of the NIH funding components.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The three members will be: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Jane L. Peterson, Ph.D.
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9305
Bethesda, MD 20892-9305
Phone: 301 496 7531
Fax: 301 480 2770
Email: Jane_Peterson@nih.gov

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9305
Rockville, MD 20852

Joni L. Rutter, PhD
Acting Director
Division of Basic Neuroscience & Behavioral Research
National Institute on Drug Abuse
6001 Executive Blvd, Rm 4282
Bethesda MD 20892-9555
Ph: 301.435.0298
Email: jrutter@nida.nih.gov

Salina Waddy, MD
Program Director
National Institute of Neurological Disorders and Stroke, NIH
Office of Clinical Research
6001 Executive Blvd, NSC, Suite 2153
Bethesda, MD 20892-9525
Rockville, MD 20852 (for Express/Courier Service)
Telephone: (301) 496-9135
FAX: (301) 402-1501
Email: waddysp@mail.nih.gov

Dr. Rudy Pozzatti, PhD
National Human Genome Research Institute
National Institutes of Health
5635 Fishers Lane, Suite 4076, MSC 9306
Bethesda, MD 20892-9306
Phone: 301-402-0838
Fax: 301 435 1580
Email: rudy.pozzatti@nih.hhs.gov

FedEx/UPS/Other Courier Delivery Address:

NIH/NHGRI/DER
5635 Fishers Lane, Suite 4076, MSC 9306
Rockville, MD 20852

Victoria Bishton
National Human Genome Research Institute
Telephone: 301.451.7928
Email: bishtonv@mail.nih.gov

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.